HDAC11 Suppresses the Thermogenic Program of Adipose Tissue via BRD2

Rushita A. Bagchi; Bradley S. Ferguson; Matthew S. Stratton; Tianjing Hu; Maria A. Cavasin; Lei Sun; Ying Hsi Lin; Dianxin Liu; Pilar Londono; Kunhua Song; Maria F. Pino; Lauren M. Sparks; Steven R. Smith; Philipp E. Scherer; Sheila Collins; Edward Seto; Timothy A. McKinsey

doi:10.1101/292011

HDAC11 Suppresses the Thermogenic Program of Adipose Tissue via BRD2

Rushita A. Bagchi, Bradley S. Ferguson, Matthew S. Stratton, Tianjing Hu, Maria A. Cavasin, Lei Sun, Ying Hsi Lin, Dianxin Liu, Pilar Londono, Kunhua Song, Maria F. Pino, Lauren M. Sparks, Steven R. Smith, Philipp E. Scherer, Sheila Collins, Edward Seto, Timothy A. McKinsey

Research output: Contribution to journal › Article › peer-review

Abstract

Little is known about the biological function of histone deacetylase 11 (HDAC11), which is the lone class IV HDAC. Here, we demonstrate that deletion of HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT). Consequently, HDAC11-deficient mice exhibit dramatically enhanced thermogenic potential and, in response to high fat feeding, attenuated obesity, insulin resistance, and hepatic steatosis. Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone binding protein. These findings define a novel epigenetic pathway for the regulation of energy homeostasis, and suggest potential for HDAC11-selective inhibitors for the treatment of obesity and diabetes.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/292011
State	Published - Mar 30 2018

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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HDAC11 Suppresses the Thermogenic Program of Adipose Tissue via BRD2. / Bagchi, Rushita A.; Ferguson, Bradley S.; Stratton, Matthew S.; Hu, Tianjing; Cavasin, Maria A.; Sun, Lei; Lin, Ying Hsi; Liu, Dianxin; Londono, Pilar; Song, Kunhua; Pino, Maria F.; Sparks, Lauren M.; Smith, Steven R.; Scherer, Philipp E.; Collins, Sheila; Seto, Edward; McKinsey, Timothy A.

In: Unknown Journal, 30.03.2018.

Research output: Contribution to journal › Article › peer-review

Bagchi, Rushita A. ; Ferguson, Bradley S. ; Stratton, Matthew S. ; Hu, Tianjing ; Cavasin, Maria A. ; Sun, Lei ; Lin, Ying Hsi ; Liu, Dianxin ; Londono, Pilar ; Song, Kunhua ; Pino, Maria F. ; Sparks, Lauren M. ; Smith, Steven R. ; Scherer, Philipp E. ; Collins, Sheila ; Seto, Edward ; McKinsey, Timothy A. / HDAC11 Suppresses the Thermogenic Program of Adipose Tissue via BRD2. In: Unknown Journal. 2018.

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title = "HDAC11 Suppresses the Thermogenic Program of Adipose Tissue via BRD2",

abstract = "Little is known about the biological function of histone deacetylase 11 (HDAC11), which is the lone class IV HDAC. Here, we demonstrate that deletion of HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT). Consequently, HDAC11-deficient mice exhibit dramatically enhanced thermogenic potential and, in response to high fat feeding, attenuated obesity, insulin resistance, and hepatic steatosis. Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone binding protein. These findings define a novel epigenetic pathway for the regulation of energy homeostasis, and suggest potential for HDAC11-selective inhibitors for the treatment of obesity and diabetes.",

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AU - Bagchi, Rushita A.

AU - Ferguson, Bradley S.

AU - Stratton, Matthew S.

AU - Hu, Tianjing

AU - Cavasin, Maria A.

AU - Sun, Lei

AU - Lin, Ying Hsi

AU - Liu, Dianxin

AU - Londono, Pilar

AU - Song, Kunhua

AU - Pino, Maria F.

AU - Sparks, Lauren M.

AU - Smith, Steven R.

AU - Scherer, Philipp E.

AU - Collins, Sheila

AU - Seto, Edward

AU - McKinsey, Timothy A.

N1 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2018/3/30

Y1 - 2018/3/30

N2 - Little is known about the biological function of histone deacetylase 11 (HDAC11), which is the lone class IV HDAC. Here, we demonstrate that deletion of HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT). Consequently, HDAC11-deficient mice exhibit dramatically enhanced thermogenic potential and, in response to high fat feeding, attenuated obesity, insulin resistance, and hepatic steatosis. Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone binding protein. These findings define a novel epigenetic pathway for the regulation of energy homeostasis, and suggest potential for HDAC11-selective inhibitors for the treatment of obesity and diabetes.

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